The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Therapy of Acute Lymphoblastic Leukemia in Children: An Evidence-Based Review

Descriptive EFS of HLA-typed patients with a sibling donor versus those with no donor. ■, sibling donor; •, no sibling donor. The EFS is adjusted for time to transplantation, WBC count, Ph chromosome status, and ploidy. Vertical lines indicate one SE above or below each plotted point. Reprinted with permission.⁵

Estimates of disease-free and overall survival (±SE) in 267 patients treated with transplantation of bone marrow from HLA-matched related donors or chemotherapy only. The curves have been adjusted for waiting time to transplantation, so that the 0 on the time axis corresponds to the median time from diagnosis to transplantation (6 months). Patients were assigned to this treatment group in a time-dependent fashion. Five-year estimates are shown. P values are from the Mantel-Byar test. P = .002 for the comparison of the 2 treatments with respect to overall survival; P < .001 for the comparison with respect to disease-free survival. Reprinted with permission.⁷

Kaplan-Meier estimates of the DFS curves in the groups of children who underwent allogeneic bone marrow transplantation (BMT) and of matched controls who underwent chemotherapy (CHEMO). Reprinted with permission.⁸

Actuarial probability of leukemia-free survival in matched cohorts of children receiving chemotherapy or undergoing transplantation, according to the duration of the first remission. Reprinted with permission.¹¹

Effect of allogeneic BMT compared with chemotherapy on EFS from the time of relapse. Descriptive curves were obtained from a Mantel-Byar analysis stratified for duration of first remission, site of relapse, and age. Because of the small number of events beyond 4 years, the dotted lines indicate the cumulative results beyond this time. Reprinted with permission.¹²

Effect of autologous BMT compared with chemotherapy on EFS from time of relapse. Descriptive curves were obtained from a Mantel-Byar analysis stratified for duration of first remission, site of relapse, and age. Because of the small number of events beyond 4 years, the dotted lines indicate the cumulative results beyond this time. Reprinted with permission.¹²

DFS rates (SE) in groups of patients who underwent an allogeneic BMT (AlloBMT; 57 patients), autologous BMT (ABMT; 36 patients), or chemotherapy (CHEMO; 230 patients) in second remission after a medullary relapse. Reprinted with permission.¹³

Kaplan-Meier survival estimates by conditioning and donor. MRD indicates matched related donor. Reprinted with permission.⁶⁹

Actuarial probability of leukemia-free survival after HLA-identical sibling bone marrow transplantation for childhood ALL, by pretransplantation conditioning regimen. Reprinted with permission.⁷⁰

Comparison of 3 conditioning regimens used for allogeneic BMT for ALL: disease-free survival. Follow-up after BMT differs because the cyclophosphamide/TBI (single-dose and fractionated) regimens were used from 1979 to 1983 (thin line), TBI/AraC was used from 1984 to 1987 (dashed line), and hyperfractionated TBI/cyclophosphamide was used from 1987 to 1991 (bold line). Reprinted with permission.⁷¹